This application addresses broad Challenge Area (04) Clinical Research and specific Challenge Topic, 04-HL- 105: Treatment of Heart Failure with Preserved Systolic Function Multiple advances in pharmacological and device therapies have been made to improve the care and outcomes for patients with heart failure and reduced left ventricular systolic function. However, the epidemiology of heart failure has been changing over the past several decades, with more than half of adults with clinically recognized heart failure syndromes currently having "preserved" left ventricular systolic function-typically defined as having a left ventricular ejection fraction of >50% or qualitative assessment of normal or preserved systolic function. Despite these changing trends and the expanding burden of heart failure, we have very few insights into any therapies that reduce the risk of premature death or heart failure exacerbation for patients with heart failure and preserved systolic function. Furthermore, we lack contemporary information on characteristics and event rates from diverse populations of patients who have heart failure with preserved systolic function that would help guide planning for future randomized clinical trials in these patients. To address these major knowledge gaps highlighted in NIH Challenge Topic 05-HL-105, we propose to leverage the National Heart, Lung and Blood Institute-sponsored Cardiovascular Research Network (CVRN), a multicenter, health plan-based research network that provides care for ~11 million members across the U.S. Through a collaboration of four participating CVRN centers, we propose to assemble a large, contemporary diverse cohort of adults with diagnosed heart failure and documented preserved left ventricular systolic function to examine the following three Specific Aims: Aim 1. To assemble a large, diverse multicenter cohort of adults with heart failure and documented preserved left ventricular systolic function between 2000-2008 and characterize recent practice patterns with available heart failure therapies. Aim 2. To determine contemporary rates and predictors of death, hospitalization for heart failure, and total resource utilization among adults with heart failure and preserved systolic function, overall and in targeted patient subgroups. Aim 3. Given the limited randomized clinical trial evidence in this population, to provide a preliminary evaluation of the effectiveness and safety of targeted therapies (i.e., ACE inhibitors, beta-blockers, and aldosterone receptor antagonists) that have been proven to be beneficial for patients with heart failure and reduced systolic function as well as exploring the outcomes associated with other commonly used therapies in chronic heart failure (e.g., diuretics, digoxin, nitrates, and statins). The public health burden for chronic heart failure is substantial-affecting 5.7 million Americans-the majority of whom are aged 65 years or older. More than half of patients with heart failure have preserved left ventricular systolic function, a condition whose prognosis remains poor and for which we have few randomized clinical trial data to guide therapy. The proposed study will provide critical and timely insights into contemporary adverse event rates and predictors of adverse outcomes, as well as into potential ways to improve the care and outcomes of the growing population of patients with heart failure and preserved systolic function.